本文選題：骨水泥　切入點(diǎn)：磁性復(fù)合材料　出處：《西南交通大學(xué)》2017年碩士論文

【摘要】：磷酸鈣骨水泥(Calcium phosphate cement,CPC)具有良好的生物安全性和可塑性,因此在骨修復(fù)領(lǐng)域得到廣泛研究。但由于其抗壓強(qiáng)度低,常用于非承重骨部位的骨修復(fù)和骨替代,使其在臨床上的應(yīng)用受到很大限制。新型納米碳材料——碳納米管(Carbon nanotubes,CNTs)和石墨烯或還原氧化石墨烯(Reduced-graphene oxide,RGO),由于具有高比表面積、優(yōu)良的力學(xué)性能、電性能等優(yōu)點(diǎn),是理想的增強(qiáng)材料。納米四氧化三鐵(Fe304)由于具有良好的磁性能、生物相容性以及材料納米效應(yīng),作為功能性納米粒子在生物醫(yī)學(xué)磁熱療、藥物靶向治療等領(lǐng)域得到廣泛應(yīng)用。因此,將Fe304與納米碳材料進(jìn)行復(fù)合,并引入到CPC體系中,可制備出具有優(yōu)良力學(xué)性能和良好磁刺激響應(yīng)性的骨修復(fù)材料。本實(shí)驗(yàn)通過(guò)水熱法在CNTs和RGO兩種碳納米材料上原位沉積Fe3O4,制備了納米碳基磁性復(fù)合材料,并研究了不同制備方法和不同表面活性劑的添加對(duì)磁性復(fù)合材料的物化性能影響。在此基礎(chǔ)上,將所制備的飽磁化強(qiáng)度較高的CNTs/Fe3O4和RGO/Fe304添加到CPC中,成功制備了磁性磷酸鈣骨水泥(MCPC),并對(duì)其物化性質(zhì)進(jìn)行了測(cè)試。并且,在不同磁強(qiáng)度的靜磁場(chǎng)作用下,深入研究添加了 CNTs/Fe3O4的MCPC在模擬體液(SBF)中的降解性能和礦化性能。通過(guò)骨髓間充質(zhì)干細(xì)胞(MSCs)與MCPC的體外共培養(yǎng)實(shí)驗(yàn),對(duì)MCPC的細(xì)胞相容性進(jìn)行了評(píng)價(jià),并探討了不同靜磁場(chǎng)強(qiáng)度的刺激對(duì)MCPC細(xì)胞相容性的影響。首先,以沸點(diǎn)回流法和水熱法,在CNTs和RGO上沉積Fe3O4制備磁性復(fù)合材料中,發(fā)現(xiàn)CNTs/Fe3O4上的Fe3O4的結(jié)晶度更高,磁性更強(qiáng);通過(guò)不同的表面活性劑對(duì)Fe304的結(jié)晶度、形貌以及在CNTs上的分散程度進(jìn)行調(diào)控;結(jié)果表明,通過(guò)添加NaAc和CTAB組合及NaAc和PEG 2000組合的表面活性劑,制得的CNTs/Fe3O4飽和磁化強(qiáng)度分別達(dá)到了 65.77emu/g和65.08emu/g,處于較高水平。將不同納米碳基磁性復(fù)合材料加入到CPC的固相粉中,成功制備了具有磁性骨水泥(MCPC)。結(jié)果表明,納米碳基磁性復(fù)合材料的添加,對(duì)MCPC的物相組成沒(méi)有影響,但會(huì)減少M(fèi)CPC的凝固時(shí)間;并且,隨著添加量的升高,MCPC的凝固時(shí)間顯著減少。不同納米碳基磁性復(fù)合材料對(duì)MCPC的影響不同,加入RGO/Fe3O4的MCPC呈現(xiàn)脆性斷裂,加入CNTs/Fe3O4的MCPC具有一定的塑性,且隨著CNTs/Fe3O4量的增加,MCPC先呈現(xiàn)出塑性斷裂,隨后呈現(xiàn)脆性斷裂。并且,加入CNTs/Fe3O4的MCPC較加入RGO/Fe3O4的MCPC的抗壓強(qiáng)度和彈性模量分別提高了 178.4%和776.5%。但CNTs/Fe3O4復(fù)合材料的添加量為9wt%時(shí),MCPC的抗壓強(qiáng)度和彈性模量均最高,分別達(dá)到40.15MPa和1782 MPa,相對(duì)于沒(méi)有添加CNTs/Fe3O4的空白CPC(BCPC)分別提高了 83.2%和93.7%。由降解與礦化實(shí)驗(yàn)可知,MCPC具有良好的防潰散能力,并且在SBF浸泡過(guò)程中,β-磷酸三鈣(β-TCP)向羥基磷灰石(HA)的轉(zhuǎn)化持續(xù)進(jìn)行。在浸泡5天后,添加了 9wt%的CNTs/Fe3O能促進(jìn)MCPC中HA晶粒在(113)晶面擇優(yōu)生長(zhǎng)。另外,CNTs/Fe3O4的添加,有利于提高M(jìn)CPC的降解速率。在靜磁場(chǎng)刺激下,MCPC的降解和礦化行為的最終結(jié)果不會(huì)發(fā)生變化,但會(huì)對(duì)其降解和礦化過(guò)程產(chǎn)生影響,主要體現(xiàn)在影響MCPC的降解和礦化速率上。其中,80m T靜磁場(chǎng)的刺激,有利于提高M(jìn)CPC的降解速率,300mT靜磁場(chǎng)的刺激,有利于提高M(jìn)CPC的礦化速率。通過(guò)體外細(xì)胞共培養(yǎng)實(shí)驗(yàn)可知,在無(wú)靜磁場(chǎng)刺激時(shí),各MCPC對(duì)MSCs細(xì)胞的增殖有抑制作用,且磁性復(fù)合材料的添加不利于MCPC上細(xì)胞胞內(nèi)Ca2+的富集,磁性復(fù)合材料的不同含量對(duì)細(xì)胞的形態(tài)沒(méi)有影響。在有靜磁場(chǎng)刺激時(shí),不同靜磁場(chǎng)刺激對(duì)BCPC上MSCs細(xì)胞的增殖活性呈現(xiàn)階段性的抑制或促進(jìn)作用;60mT靜磁場(chǎng)的刺激對(duì)MCPC上MSCs細(xì)胞的增殖活性均有較明顯的促進(jìn)作用,當(dāng)磁性復(fù)合材料添加量為9wt%時(shí)促進(jìn)作用最為明顯;不同靜磁場(chǎng)刺激均對(duì)MCPC上MSCs細(xì)胞的分化有促進(jìn)作用,且在130mT靜磁場(chǎng)作用下,當(dāng)添加量為12wt%時(shí),MCPC上MSCs細(xì)胞的分化活性最高。不同靜磁場(chǎng)刺激均能促進(jìn)MCPC上MSCs細(xì)胞的黏附和鋪展。不同靜磁場(chǎng)刺激均不利于BCPC上細(xì)胞胞內(nèi)Ca2+富集,且磁強(qiáng)越大,富集程度越低。不同靜磁場(chǎng)刺激均能促進(jìn)磁性復(fù)合材料含量為9wt%的MCPC上細(xì)胞對(duì)Ca2+的富集,且磁強(qiáng)越大,富集程度越高,但促進(jìn)作用存在閥值。表明MCPC對(duì)MSCs細(xì)胞的影響具有磁響應(yīng)性,并且其細(xì)胞相容性具有"窗口"效應(yīng)。
[Abstract]:Calcium phosphate cement (Calcium phosphate, cement, CPC) has a good biocompatibility and plasticity, so it has been widely studied in the field of bone repair. But because of its low compressive strength, commonly used in non weight bearing bone bone repair and bone substitute, so its clinical application is limited. The new nano carbon material: carbon nanotubes (Carbon, nanotubes, CNTs) and graphene or graphene (Reduced-graphene oxide RGO), because of its high surface area, excellent mechanical properties, electrical properties and other advantages, is the ideal material. Enhancement of Fe3O4 nanoparticles (Fe304) with good magnetic properties, biocompatibility and material the effect of nano, as functional nanoparticles in biomedical magnetic hyperthermia, drug targeting and other fields are widely used. Therefore, Fe304 and nano carbon composite materials, and introduced into the CPC system, Can be prepared by stimulus response of bone repair materials with excellent mechanical properties and good magnetic. The experimental hydrothermal method by CNTs and RGO in two kinds of carbon nano materials in situ deposition Fe3O4, nano carbon based magnetic composite material was prepared, and studied the effects of different preparation methods and different surfactants. Add the physicochemical properties of the composite materials. On this basis, CNTs/Fe3O4 and RGO/Fe304 with high magnetization prepared will be added to the CPC, the magnetic calcium phosphate cement (MCPC) was prepared, and its physicochemical properties were tested. Furthermore, in static magnetic field with different magnetic intensity under the in-depth study of adding CNTs/Fe3O4 MCPC in simulated body fluid (SBF) in the degradation and mineralization properties. Through bone marrow mesenchymal stem cells (MSCs) and MCPC co cultured in vitro experiments on the biocompatibility of MCPC was evaluated, and discussed. With static magnetic field stimulation compatibility effects on MCPC cells. Firstly, by boiling reflux method and hydrothermal method, CNTs and RGO on the deposition of Fe3O4 in preparation of magnetic composite materials, found on the crystallization of CNTs/Fe3O4 Fe3O4 degrees higher, stronger magnetic; by crystallization of different surfactants on the degree of Fe304, morphology and dispersion degree of CNTs in the regulation; results show that by adding surface active NaAc and CTAB and NaAc and PEG 2000 combination agent, prepared by CNTs/Fe3O4 saturation magnetization reached 65.77emu/g and 65.08emu/g, at a high level. The different carbon based magnetic composite material is added into solid powder CPC in the successful preparation of the magnetic bone cement (MCPC). The results show that the addition of nano carbon based magnetic composite materials of MCPC, the phase composition has no effect, but will reduce the setting time of MCPC; and, with the amount of Increased coagulation time was significantly reduced. MCPC effects of different nano carbon based magnetic composite materials of MCPC different, adding RGO/Fe3O4 MCPC showed brittle fracture, adding CNTs/Fe3O4 MCPC has certain plasticity, and with the increase of CNTs/Fe3O4 content, MCPC first showed ductile fracture and brittle fracture. Then the compressive strength. And the elastic modulus of MCPC was added into CNTs/Fe3O4 RGO/Fe3O4 MCPC and 776.5%. were increased by 178.4% but the amount of CNTs/Fe3O4 composites was 9wt%, compressive strength and elastic modulus of MCPC was the highest, reached 40.15MPa and 1782 MPa respectively, compared with no added CNTs/Fe3O4 blank CPC (BCPC) were increased by 83.2% and by 93.7%. degradation and mineralization experiment shows that MCPC has good ability of anti collapsibility, and SBF in the soaking process, beta tricalcium phosphate (beta -TCP) to hydroxyapatite (HA) transformed into continuous In line. After 5 days of immersion, adding 9wt% CNTs/Fe3O could promote the MCPC in the HA grain in the (113) preferred growth. In addition, the addition of CNTs/Fe3O4 can improve the degradation rate of MCPC. In the static magnetic field stimulation, the final result of MCPC degradation and mineralization behavior will not change, but the impact the degradation and mineralization process, mainly reflected in the influence of MCPC degradation and mineralization rate. Among them, 80m T static magnetic field stimulation, can improve the degradation rate of MCPC and 300mT static magnetic field stimulation, can improve the mineralization rate of MCPC. Through the experiment in vitro, in the absence of static magnetic field stimulation, inhibit the MCPC proliferation of MSCs cells, and the addition of magnetic composite materials for MCPC on the intracellular Ca2+ accumulation, did not affect the content of different forms of magnetic composite materials of cells. In a static magnetic field stimulation, different static Magnetic stimulation on BCPC MSCs cell proliferation activity showed phasic inhibition or facilitation; promote the proliferation activity of 60mT static magnetic field stimulation on MCPC MSCs cells obviously, when the magnetic composite dosage 9wt% the most obvious role; promote the stimulation of different static magnetic field of MCPC on the differentiation of MSCs cells, and the static magnetic field in 130mT, when the dosage is 12wt%, MCPC on the differentiation of MSCs cells. The highest activity of different static magnetic stimulation can promote cell adhesion and spreading of MSCs cells MCPC. Stimulation of different static magnetic field are not conducive to BCPC on the intracellular accumulation of Ca2+, and the strong magnetic the greater the enrichment, the lower degree of different static magnetic stimulation can promote the content of magnetic composite materials for the enrichment of Ca2+ 9wt% on MCPC cells, and the magnetic intensity is strong, the higher the degree of enrichment, but the role of MSCs MCPC. That there is a threshold of fine The effect of the cell is magnetic responsiveness, and its cell compatibility has a "window" effect.

【學(xué)位授予單位】：西南交通大學(xué)
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2017
【分類號(hào)】：TB33;R318.08

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